The overall goals of the Case Center for Transdisciplinary Research on Energetics and Cancer are defined organizationally and scientifically. Organizationally, we seek 1) to establish a productive, durable program for transdisciplinary research on energetics and cancer at Case University, 2) to provide pilot project support and training opportunities for new and established scientists who can conduct integrative research on energetics, energy balance and their consequences relative to cancer across the continuum from cancer causation and prevention through survival, and 3) to establish collaborative relations with investigators throughout our university and at other TREC Centers and universities to maximally and synergistically utilize resources to significantly impact problems associated with obesity and cancer. Scientifically, we will conduct a spectrum of mechanism-based laboratory, clinical, and population-based studies to identify targets for prevention and control of obesity and interruption of the linkage between obesity and cancer. The scientific aims are defined by three programs and two pilot projects which are highly interactive and are supported by three TREC core facilities and by the 17 Comprehensive Cancer Center core facilities. Project 1 seeks to determine the intestinal tumor-inducing effect and molecular signaling pathways associated with high-fat diet versus obesity in unique strains of mice with chromosomal substitutions rendering them susceptible or resistant to the obesigenic effects of hig hfat diets. Project 2 will examine candidate gene variance and haplotype, associated biomarkers, and insulin-resistance syndrome related serum markers to understand how insulin-resistance syndrome, related genes and dietary factors work in concert in the etiology of human colon neoplasia. Project 3 will investigate determinants of obesity and metabolic dysfunction during the critical life-transition period of adolescence. This study will capitalize on a unique population cohort followed as part of the Cleveland Children's Sleep and Health Study and will investigate sleep phenotype and sleep disturbances as a novel and important determinant of obesity and its relation to metabolic dysfunction. Pilot Project 1 will investigate the role of ER stress pathways linking the metabolic stress of obesity to development of insulin resistance, its consequences and the identification of molecular targets for interrupting these pathways to prevent health consequences of obesity.